The purpose of this project is the development of a clinical, non-invasive monitor of tissue blood flow by analysis of the spectrum of Doppler-scattered laser light. The NIH Laser Doppler Blood Flow Monitor has been demonstrated to be highly portable and clinically convenient with sterilizable, rugged flexible 4m fiber optic probes and portable photodiode detection system. The linearity of the flow analysis processor has been demonstrated in a variety of tissues and clearly resolves physiologic flow changes including pulsatile flow in the microcirculation. Muscle blood flow in over 50 patients with neuromuscular disease has been studied and data suggest that post occlusive reactive hyperemia responses may be primary or secondary indicators of disease state. Measurements of local muscle blood flow dynamics in patients with neuromuscular diseases indicate abnormalities distinct to different disease types. Nasal blood flow has been shown to be a quantitative measure of the physiologic response of the nose to drug challenges. Brain and spinal cord blood flow measurements during microsurgery has been shown to be feasible in two patients and provides the surgeon with potential for useful evaluation of his surgical procedures as well as for furthering understanding of microcirculatory dynamics in neural tissue. Studies show a characteristic local oscillatory flow pattern in a capillary microcirculation of the skin in sickle cell patients which appears to correlate with severity of disease and its response to drug therapy. Similar oscillations presumably due to myogenic arteriolar smooth muscle vasomotion are characteristic of several hypertensive patients, particularly those on drugs inducing peripheral vasoconstriction. Preliminary studies on patients with Type I diabetes have shown abnormalities potentially related to the etiology of the microvascular component of long-term type I diabetes. In summary numerous ongoing clinical studies seek to characterize microvascular functional abnormalities and their role in a number of diseases with microvascular components.